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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-10-29 21:50:43 UTC
HMDB IDHMDB00254
Secondary Accession NumbersNone
Metabolite Identification
Common NameSuccinic acid
DescriptionSuccinic acid is a dicarboxylic acid. The anion, succinate, is a component of the citric acid cycle capable of donating electrons to the electron transfer chain. Succinate dehydrogenase (SDH) plays an important role in the mitochondria, being both part of the respiratory chain and the Krebs cycle. SDH with a covalently attached FAD prosthetic group, binds enzyme substrates (succinate and fumarate) and physiological regulators (oxaloacetate and ATP). Oxidizing succinate links SDH to the fast-cycling Krebs cycle portion where it participates in the breakdown of acetyl-CoA throughout the whole Krebs cycle. The succinate can readily be imported into the mitochondrial matrix by the n-butylmalonate- (or phenylsuccinate-) sensitive dicarboxylate carrier in exchange with inorganic phosphate or another organic acid, e. g. malate. (PMID 16143825 ) Mutations in the four genes encoding the subunits of the mitochondrial respiratory chain succinate dehydrogenase are associated with a wide spectrum of clinical presentations (i.e.: Huntington's disease. (PMID 11803021 ).
Structure
Thumb
Synonyms
  1. 1,2-Ethanedicarboxylate
  2. 1,2-Ethanedicarboxylic acid
  3. 1,4-Butanedioate
  4. 1,4-Butanedioic acid
  5. Amber acid
  6. Asuccin
  7. Dihydrofumarate
  8. Dihydrofumaric acid
  9. Katasuccin
  10. Succinate
  11. Wormwood acid
Chemical FormulaC4H6O4
Average Molecular Weight118.088
Monoisotopic Molecular Weight118.02660868
IUPAC Namebutanedioic acid
Traditional Namesuccinic acid
CAS Registry Number110-15-6
SMILES
OC(=O)CCC(O)=O
InChI Identifier
InChI=1S/C4H6O4/c5-3(6)1-2-4(7)8/h1-2H2,(H,5,6)(H,7,8)
InChI KeyKDYFGRWQOYBRFD-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassOrganic Acids and Derivatives
ClassCarboxylic Acids and Derivatives
Sub ClassDicarboxylic Acids and Derivatives
Other Descriptors
  • Aliphatic Acyclic Compounds
  • Dicarboxylic acids(Lipidmaps)
  • Fatty Acids and Conjugates
  • alpha,omega-dicarboxylic acid(ChEBI)
Substituents
  • Carboxylic Acid
Direct ParentDicarboxylic Acids and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
  • Microbial
Biofunction
  • Component of Arginine and proline metabolism
  • Component of Butanoate metabolism
  • Component of C5-Branched dibasic acid metabolism
  • Component of Glutamate metabolism
  • Component of Propanoate metabolism
  • DNA component
ApplicationNot Available
Cellular locations
  • Extracellular
  • Mitochondria
  • Endoplasmic reticulum
  • Peroxisome
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point185 - 188 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility83.2 mg/mLNot Available
LogP-0.59HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility211 g/LALOGPS
logP-0.53ALOGPS
logP-0.4ChemAxon
logS0.25ALOGPS
pKa (Strongest Acidic)3.55ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area74.6ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity23.54ChemAxon
Polarizability10.16ChemAxon
Spectra
SpectraGC-MSMS/MSLC-MS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Extracellular
  • Mitochondria
  • Endoplasmic reticulum
  • Peroxisome
Biofluid Locations
  • Blood
  • Cerebrospinal Fluid (CSF)
  • Saliva
  • Urine
Tissue Location
  • Adipose Tissue
  • Brain
  • Fibroblasts
  • Kidney
  • Liver
  • Muscle
  • Pancreas
  • Placenta
  • Prostate
  • Skeletal Muscle
  • Spleen
Pathways
NameSMPDB LinkKEGG Link
Carnitine SynthesisSMP00465Not Available
Citric Acid CycleSMP00057map00020
Glutamate MetabolismSMP00072map00250
Mitochondrial Electron Transport ChainSMP00355map00190
Phytanic Acid Peroxisomal OxidationSMP00450Not Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified16.0 (0.00-32.0) uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified23.5 uMAdult (>18 years old)Not SpecifiedNormal details
BloodDetected and Quantified8.8 +/- 2.7 uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
Cerebrospinal Fluid (CSF)Detected and Quantified47.2 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified19 uMAdult (>18 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified150.0 +/- 110.0 uMElderly (>65 years old)BothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified3 +/- 2 uMNot SpecifiedBothNormal details
Cerebrospinal Fluid (CSF)Detected and Quantified28.5 (24-33) uMAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
Cerebrospinal Fluid (CSF)Detected and Quantified3.0 +/- 2.0 uMAdult (>18 years old)BothNormal details
SalivaDetected and Quantified125.15 +/- 180.60 uMAdult (>18 years old)BothNormal
    • Dame, ZT. et al. ...
details
SalivaDetected and Quantified2260 (60.0-4460) uMAdult (>18 years old)BothNormal details
SalivaDetected and Quantified14 (2-112) uMAdult (>18 years old)Male
Normal
details
SalivaDetected and Quantified9 (1-78) uMAdult (>18 years old)Male
Normal
details
SalivaDetected and Quantified21 (<1-66) uMAdult (>18 years old)Male
Normal
details
SalivaDetected and Quantified9 (<1-54) uMAdult (>18 years old)Female
Normal
details
SalivaDetected and Quantified9.03 +/- 5.22 uMAdult (>18 years old)Female
Normal
    • Sugimoto et al. (...
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected and Quantified15.0 +/- 15.5 uMAdult (>18 years old)Not Specified
Normal
    • Sugimoto et al. (...
details
SalivaDetected and Quantified15.6 +/- 27.7 uMAdult (>18 years old)Not Specified
Normal
    • Sugimoto et al. (...
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
SalivaDetected and Quantified24.3 +/- 20.4 uMAdult (>18 years old)Male
Normal
    • Sugimoto et al. (...
details
SalivaDetected and Quantified4-145 uMAdult (>18 years old)Male
normal
details
SalivaDetected and Quantified1-33 uMAdult (>18 years old)Male
normal
details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)MaleNormal details
UrineDetected and Quantified4.7 (1.1-14.5) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified12.60 +/- 12.13 umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified14.48 +/- 3.20 umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)Both
Normal
details
UrineDetected and Quantified7.7 (1.9-20.0) umol/mmol creatinineAdolescent (13-18 years old)BothNormal details
UrineDetected and Quantified3.8 (1.25-6.7) umol/mmol creatinineAdult (>18 years old)BothNormal
    • Geigy Scientific ...
details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)BothNormal details
UrineDetected and Quantified2.10 umol/mmol creatinineAdult (>18 years old)BothNormal
    • Shaykhutdinov RA,...
details
UrineDetected and Quantified9.9 +/- 5.0 umol/mmol creatinineAdult (>18 years old)MaleNormal details
UrineDetected and Quantified14.4 +/- 4.9 umol/mmol creatinineAdult (>18 years old)FemaleNormal details
UrineDetected and Quantified7.5 (0.5-16) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified6.0 (0.3-33.3) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
UrineDetected but not QuantifiedNot ApplicableAdult (>18 years old)Male
Normal
details
UrineDetected and Quantified5.6 +/- 3.8 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified197.2 (29.4-486.2) umol/mmol creatinineNewborn (0-30 days old)BothNormal details
UrineDetected and Quantified185.4 (6.0-342.6) umol/mmol creatinineInfant (0-1 year old)BothNormal details
UrineDetected and Quantified11.6 (4.0-27.3) umol/mmol creatinineChildren (1-13 years old)BothNormal details
UrineDetected and Quantified8.25 (0.5-16.0) umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified1.3 umol/mmol creatinineAdult (>18 years old)BothNormal details
UrineDetected and Quantified6.2 (2.5-13.5) umol/mmol creatinineAdult (>18 years old)Both
Normal
details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
Cerebrospinal Fluid (CSF)Detected and Quantified19.0 (0.0-38.0) uMAdult (>18 years old)BothCanavan Disease details
Cerebrospinal Fluid (CSF)Detected and Quantified55.0 (19.0-91.0) uMAdult (>18 years old)BothAlzheimer's disease details
UrineDetected and Quantified43.35 +/- 25.08 umol/mmol creatinineChildren (1-13 years old)BothMalnutrition (type kwashiorkor and marasmus) details
UrineDetected and Quantified9.0 +/- 6.0 umol/mmol creatinineAdult (>18 years old)BothLung cancer details
Associated Disorders and Diseases
Disease References
Alzheimer's disease
  1. Redjems-Bennani N, Jeandel C, Lefebvre E, Blain H, Vidailhet M, Gueant JL: Abnormal substrate levels that depend upon mitochondrial function in cerebrospinal fluid from Alzheimer patients. Gerontology. 1998;44(5):300-4. Pubmed: 9693263
Canavan disease
  1. Wevers RA, Engelke U, Wendel U, de Jong JG, Gabreels FJ, Heerschap A: Standardized method for high-resolution 1H-NMR of cerebrospinal fluid. Clin Chem. 1995 May;41(5):744-51. Pubmed: 7729054
Lung Cancer
  1. Wishart DS, Knox C, Guo AC, Eisner R, Young N, Gautam B, Hau DD, Psychogios N, Dong E, Bouatra S, Mandal R, Sinelnikov I, Xia J, Jia L, Cruz JA, Lim E, Sobsey CA, Shrivastava S, Huang P, Liu P, Fang L, Peng J, Fradette R, Cheng D, Tzur D, Clements M, Lewis A, De Souza A, Zuniga A, Dawe M, Xiong Y, Clive D, Greiner R, Nazyrova A, Shaykhutdinov R, Li L, Vogel HJ, Forsythe I: HMDB: a knowledgebase for the human metabolome. Nucleic Acids Res. 2008 Oct 25. Pubmed: 18953024
Associated OMIM IDs
DrugBank IDDB00139
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB001931
KNApSAcK IDC00001205
Chemspider ID1078
KEGG Compound IDC00042
BioCyc IDSUC
BiGG ID33633
Wikipedia LinkSuccinic acid
NuGOwiki LinkHMDB00254
Metagene LinkHMDB00254
METLIN ID114
PubChem Compound1110
PDB IDSIN
ChEBI ID15741
References
Synthesis ReferenceBerglund, Kris Arvid; Andersson, Christian; Rova, Ulrika. Process for the production of succinic acid. PCT Int. Appl. (2007), 30pp.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. Pubmed: 19212411
  2. Guneral F, Bachmann C: Age-related reference values for urinary organic acids in a healthy Turkish pediatric population. Clin Chem. 1994 Jun;40(6):862-6. Pubmed: 8087979
  3. Hoffmann GF, Meier-Augenstein W, Stockler S, Surtees R, Rating D, Nyhan WL: Physiology and pathophysiology of organic acids in cerebrospinal fluid. J Inherit Metab Dis. 1993;16(4):648-69. Pubmed: 8412012
  4. Silwood CJ, Lynch E, Claxson AW, Grootveld MC: 1H and (13)C NMR spectroscopic analysis of human saliva. J Dent Res. 2002 Jun;81(6):422-7. Pubmed: 12097436
  5. Redjems-Bennani N, Jeandel C, Lefebvre E, Blain H, Vidailhet M, Gueant JL: Abnormal substrate levels that depend upon mitochondrial function in cerebrospinal fluid from Alzheimer patients. Gerontology. 1998;44(5):300-4. Pubmed: 9693263
  6. Wevers RA, Engelke U, Wendel U, de Jong JG, Gabreels FJ, Heerschap A: Standardized method for high-resolution 1H-NMR of cerebrospinal fluid. Clin Chem. 1995 May;41(5):744-51. Pubmed: 7729054
  7. Magera MJ, Helgeson JK, Matern D, Rinaldo P: Methylmalonic acid measured in plasma and urine by stable-isotope dilution and electrospray tandem mass spectrometry. Clin Chem. 2000 Nov;46(11):1804-10. Pubmed: 11067816
  8. Zhang TM, Sener A, Malaisse WJ: Hydrolysis of succinic acid dimethyl ester in rat pancreatic islets. Biochem Mol Med. 1995 Aug;55(2):131-7. Pubmed: 7582870
  9. Groenen PM, Engelke UF, Wevers RA, Hendriks JC, Eskes TK, Merkus HM, Steegers-Theunissen RP: High-resolution 1H NMR spectroscopy of amniotic fluids from spina bifida fetuses and controls. Eur J Obstet Gynecol Reprod Biol. 2004 Jan 15;112(1):16-23. Pubmed: 14687733
  10. Meijer-Severs GJ, van Santen E: Short-chain fatty acids and succinate in feces of healthy human volunteers and their correlation with anaerobe cultural counts. Scand J Gastroenterol. 1987 Aug;22(6):672-6. Pubmed: 3659829
  11. Ren LC, Huang XY, Long JH: [Effects of succinic acid on the function of in vitro cultured human fibroblasts] Zhonghua Shao Shang Za Zhi. 2004 Feb;20(1):34-6. Pubmed: 15059451
  12. Wevers RA, Engelke U, Heerschap A: High-resolution 1H-NMR spectroscopy of blood plasma for metabolic studies. Clin Chem. 1994 Jul;40(7 Pt 1):1245-50. Pubmed: 8013094
  13. Borenstein DG, Gibbs CA, Jacobs RP: Gas-liquid chromatographic analysis of synovial fluid: volatile short-chain fatty acids in septic arthritis. Ann Rheum Dis. 1983 Aug;42(4):362-7. Pubmed: 6882030
  14. Frenkel G, Peterson RN, Freund M: Oxidative and glycolytic metabolism of semen components by washed guinea pig spermatozoa. Fertil Steril. 1975 Feb;26(2):144-7. Pubmed: 1126459
  15. Briere JJ, Favier J, El Ghouzzi V, Djouadi F, Benit P, Gimenez AP, Rustin P: Succinate dehydrogenase deficiency in human. Cell Mol Life Sci. 2005 Oct;62(19-20):2317-24. Pubmed: 16143825
  16. Rustin P, Rotig A: Inborn errors of complex II--unusual human mitochondrial diseases. Biochim Biophys Acta. 2002 Jan 17;1553(1-2):117-22. Pubmed: 11803021

Enzymes

General function:
Involved in succinate dehydrogenase activity
Specific function:
Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
Gene Name:
SDHC
Uniprot ID:
Q99643
Molecular weight:
16650.185
Reactions
Ubiquinone-2 + Succinic acid → QH2 + Fumaric aciddetails
References
  1. Bayley JP, van Minderhout I, Weiss MM, Jansen JC, Oomen PH, Menko FH, Pasini B, Ferrando B, Wong N, Alpert LC, Williams R, Blair E, Devilee P, Taschner PE: Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma. BMC Med Genet. 2006 Jan 11;7:1. Pubmed: 16405730
  2. Leibowitz G, Khaldi MZ, Shauer A, Parnes M, Oprescu AI, Cerasi E, Jonas JC, Kaiser N: Mitochondrial regulation of insulin production in rat pancreatic islets. Diabetologia. 2005 Aug;48(8):1549-59. Epub 2005 Jun 29. Pubmed: 15986240
  3. Bayley JP, Devilee P, Taschner PE: The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency. BMC Med Genet. 2005 Nov 16;6:39. Pubmed: 16288654
  4. Szeto SS, Reinke SN, Sykes BD, Lemire BD: Ubiquinone-binding site mutations in the Saccharomyces cerevisiae succinate dehydrogenase generate superoxide and lead to the accumulation of succinate. J Biol Chem. 2007 Sep 14;282(37):27518-26. Epub 2007 Jul 18. Pubmed: 17636259
  5. Kubo Y, Takagi H, Nakamori S: Effect of gene disruption of succinate dehydrogenase on succinate production in a sake yeast strain. J Biosci Bioeng. 2000;90(6):619-24. Pubmed: 16232921
General function:
Involved in electron carrier activity
Specific function:
Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q). Can act as a tumor suppressor.
Gene Name:
SDHA
Uniprot ID:
P31040
Molecular weight:
72690.975
Reactions
Succinic acid + Coenzyme Q10 → Fumaric acid + QH(2)details
Ubiquinone-2 + Succinic acid → QH2 + Fumaric aciddetails
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
  3. Maklashina E, Iverson TM, Sher Y, Kotlyar V, Andrell J, Mirza O, Hudson JM, Armstrong FA, Rothery RA, Weiner JH, Cecchini G: Fumarate reductase and succinate oxidase activity of Escherichia coli complex II homologs are perturbed differently by mutation of the flavin binding domain. J Biol Chem. 2006 Apr 21;281(16):11357-65. Epub 2006 Feb 15. Pubmed: 16484232
  4. Takeo S, Kokaze A, Ng CS, Mizuchi D, Watanabe JI, Tanabe K, Kojima S, Kita K: Succinate dehydrogenase in Plasmodium falciparum mitochondria: molecular characterization of the SDHA and SDHB genes for the catalytic subunits, the flavoprotein (Fp) and iron-sulfur (Ip) subunits. Mol Biochem Parasitol. 2000 Apr 15;107(2):191-205. Pubmed: 10779596
  5. Ackrell BA: Cytopathies involving mitochondrial complex II. Mol Aspects Med. 2002 Oct;23(5):369-84. Pubmed: 12231007
General function:
Involved in iron ion binding
Specific function:
Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q) (By similarity).
Gene Name:
SDHD
Uniprot ID:
O14521
Molecular weight:
17042.82
Reactions
Ubiquinone-2 + Succinic acid → QH2 + Fumaric aciddetails
References
  1. Brink I, Schaefer O, Walz M, Neumann HP: Fluorine-18 DOPA PET imaging of paraganglioma syndrome. Clin Nucl Med. 2006 Jan;31(1):39-41. Pubmed: 16374125
  2. Sun F, Huo X, Zhai Y, Wang A, Xu J, Su D, Bartlam M, Rao Z: Crystal structure of mitochondrial respiratory membrane protein complex II. Cell. 2005 Jul 1;121(7):1043-57. Pubmed: 15989954
  3. Bayley JP, Devilee P, Taschner PE: The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency. BMC Med Genet. 2005 Nov 16;6:39. Pubmed: 16288654
  4. Lehtonen HJ, Makinen MJ, Kiuru M, Laiho P, Herva R, van Minderhout I, Hogendoorn PC, Cornelisse C, Devilee P, Launonen V, Aaltonen LA: Increased HIF1 alpha in SDH and FH deficient tumors does not cause microsatellite instability. Int J Cancer. 2007 Sep 15;121(6):1386-9. Pubmed: 17520677
  5. Bayley JP, van Minderhout I, Weiss MM, Jansen JC, Oomen PH, Menko FH, Pasini B, Ferrando B, Wong N, Alpert LC, Williams R, Blair E, Devilee P, Taschner PE: Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma. BMC Med Genet. 2006 Jan 11;7:1. Pubmed: 16405730
General function:
Involved in electron carrier activity
Specific function:
Iron-sulfur protein (IP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
Gene Name:
SDHB
Uniprot ID:
P21912
Molecular weight:
31629.365
Reactions
Succinic acid + Coenzyme Q10 → Fumaric acid + QH(2)details
Ubiquinone-2 + Succinic acid → QH2 + Fumaric aciddetails
References
  1. Arikawa Y, Kuroyanagi T, Shimosaka M, Muratsubaki H, Enomoto K, Kodaira R, Okazaki M: Effect of gene disruptions of the TCA cycle on production of succinic acid in Saccharomyces cerevisiae. J Biosci Bioeng. 1999;87(1):28-36. Pubmed: 16232421
  2. Bayley JP, Devilee P, Taschner PE: The SDH mutation database: an online resource for succinate dehydrogenase sequence variants involved in pheochromocytoma, paraganglioma and mitochondrial complex II deficiency. BMC Med Genet. 2005 Nov 16;6:39. Pubmed: 16288654
  3. Lehtonen HJ, Makinen MJ, Kiuru M, Laiho P, Herva R, van Minderhout I, Hogendoorn PC, Cornelisse C, Devilee P, Launonen V, Aaltonen LA: Increased HIF1 alpha in SDH and FH deficient tumors does not cause microsatellite instability. Int J Cancer. 2007 Sep 15;121(6):1386-9. Pubmed: 17520677
  4. Bayley JP, van Minderhout I, Weiss MM, Jansen JC, Oomen PH, Menko FH, Pasini B, Ferrando B, Wong N, Alpert LC, Williams R, Blair E, Devilee P, Taschner PE: Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma. BMC Med Genet. 2006 Jan 11;7:1. Pubmed: 16405730
  5. Szeto SS, Reinke SN, Sykes BD, Lemire BD: Ubiquinone-binding site mutations in the Saccharomyces cerevisiae succinate dehydrogenase generate superoxide and lead to the accumulation of succinate. J Biol Chem. 2007 Sep 14;282(37):27518-26. Epub 2007 Jul 18. Pubmed: 17636259
General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
Gene Name:
ALDH5A1
Uniprot ID:
P51649
Molecular weight:
57214.23
Reactions
Succinic acid semialdehyde + NAD + Water → Succinic acid + NADHdetails
Succinic acid semialdehyde + NAD + Water → Succinic acid + NADH + Hydrogen Iondetails
References
  1. Yogeeswari P, Sriram D, Vaigundaragavendran J: The GABA shunt: an attractive and potential therapeutic target in the treatment of epileptic disorders. Curr Drug Metab. 2005 Apr;6(2):127-39. Pubmed: 15853764
  2. Popov VN, Eprintsev AT, Fedorin DN, Fomenko OIu, Igamberdiev AU: [Role of transamination in the mobilization of respiratory substrates in germinating seeds of castor oil plants]. Prikl Biokhim Mikrobiol. 2007 May-Jun;43(3):376-81. Pubmed: 17619587
  3. Wang C, Zhang HB, Wang LH, Zhang LH: Succinic semialdehyde couples stress response to quorum-sensing signal decay in Agrobacterium tumefaciens. Mol Microbiol. 2006 Oct;62(1):45-56. Epub 2006 Aug 30. Pubmed: 16942602
  4. Ahn SJ, Yang CH, Cooksey DA: Pseudomonas putida 06909 genes expressed during colonization on mycelial surfaces and phenotypic characterization of mutants. J Appl Microbiol. 2007 Jul;103(1):120-32. Pubmed: 17584458
  5. Chiribau CB, Mihasan M, Ganas P, Igloi GL, Artenie V, Brandsch R: Final steps in the catabolism of nicotine. FEBS J. 2006 Apr;273(7):1528-36. Pubmed: 16689938
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed: 11752352
General function:
Involved in electron carrier activity
Specific function:
Converts phytanoyl-CoA to 2-hydroxyphytanoyl-CoA.
Gene Name:
PHYH
Uniprot ID:
O14832
Molecular weight:
38538.065
Reactions
Phytanoyl-CoA + Oxoglutaric acid + Oxygen → 2-Hydroxyphytanoyl-CoA + Succinic acid + CO(2)details
General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
Gene Name:
P4HA2
Uniprot ID:
O15460
Molecular weight:
60632.19
Reactions
L-proline-[procollagen] + Oxoglutaric acid + Oxygen → trans-4-hydroxy-L-proline-[procollagen] + Succinic acid + CO(2)details
L-Proline + Oxoglutaric acid + Oxygen → 4-Hydroxyproline + Succinic acid + Carbon dioxidedetails
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
Gene Name:
P4HA1
Uniprot ID:
P13674
Molecular weight:
60966.645
Reactions
L-proline-[procollagen] + Oxoglutaric acid + Oxygen → trans-4-hydroxy-L-proline-[procollagen] + Succinic acid + CO(2)details
L-Proline + Oxoglutaric acid + Oxygen → 4-Hydroxyproline + Succinic acid + Carbon dioxidedetails
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
General function:
Involved in iron ion binding
Specific function:
Catalyzes the formation of L-carnitine from gamma-butyrobetaine.
Gene Name:
BBOX1
Uniprot ID:
O75936
Molecular weight:
44714.6
Reactions
4-Trimethylammoniobutanoic acid + Oxoglutaric acid + Oxygen → L-Carnitine + Succinic acid + CO(2)details
4-Trimethylammoniobutanoic acid + Oxoglutaric acid + Oxygen → L-Carnitine + Succinic acid + Carbon dioxidedetails
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
  3. Yoshisue K, Yamamoto Y, Yoshida K, Saeki M, Minami Y, Esumi Y, Kawaguchi Y: Pharmacokinetics and biological fate of 3-(2,2, 2-trimethylhydrazinium)propionate dihydrate (MET-88), a novel cardioprotective agent, in rats. Drug Metab Dispos. 2000 Jun;28(6):687-94. Pubmed: 10820142
General function:
Involved in oxidoreductase activity
Specific function:
Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens. These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links.
Gene Name:
PLOD1
Uniprot ID:
Q02809
Molecular weight:
83549.55
Reactions
L-lysine-[procollagen] + Oxoglutaric acid + Oxygen → (2S,5R)-5-hydroxy-L-lysine-[procollagen] + Succinic acid + CO(2)details
Protein lysine + Oxoglutaric acid + Oxygen → Procollagen 5-hydroxy-L-lysine + Succinic acid + Carbon dioxide + Waterdetails
References
  1. Cudic M, Patel DA, Lauer-Fields JL, Brew K, Fields GB: Development of a convenient peptide-based assay for lysyl hydroxylase. Biopolymers. 2008;90(3):330-8. Pubmed: 17610258
General function:
Involved in oxidoreductase activity
Specific function:
Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens. These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links.
Gene Name:
PLOD2
Uniprot ID:
O00469
Molecular weight:
84685.07
Reactions
L-lysine-[procollagen] + Oxoglutaric acid + Oxygen → (2S,5R)-5-hydroxy-L-lysine-[procollagen] + Succinic acid + CO(2)details
Protein lysine + Oxoglutaric acid + Oxygen → Procollagen 5-hydroxy-L-lysine + Succinic acid + Carbon dioxide + Waterdetails
General function:
Involved in oxidoreductase activity
Specific function:
Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens. These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links.
Gene Name:
PLOD3
Uniprot ID:
O60568
Molecular weight:
84784.505
Reactions
L-lysine-[procollagen] + Oxoglutaric acid + Oxygen → (2S,5R)-5-hydroxy-L-lysine-[procollagen] + Succinic acid + CO(2)details
Protein lysine + Oxoglutaric acid + Oxygen → Procollagen 5-hydroxy-L-lysine + Succinic acid + Carbon dioxide + Waterdetails
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
General function:
Involved in CoA-transferase activity
Specific function:
Key enzyme for ketone body catabolism. Transfers the CoA moiety from succinate to acetoacetate. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate.
Gene Name:
OXCT1
Uniprot ID:
P55809
Molecular weight:
56157.175
Reactions
Succinyl-CoA + a 3-oxo acid → Succinic acid + a 3-oxoacyl-CoAdetails
Succinyl-CoA + Acetoacetic acid → Succinic acid + Acetoacetyl-CoAdetails
References
  1. Coros AM, Swenson L, Wolodko WT, Fraser ME: Structure of the CoA transferase from pig heart to 1.7 A resolution. Acta Crystallogr D Biol Crystallogr. 2004 Oct;60(Pt 10):1717-25. Epub 2004 Sep 23. Pubmed: 15388917
General function:
Involved in CoA-transferase activity
Specific function:
Key enzyme for ketone body catabolism. Transfers the CoA moiety from succinate to acetoacetate. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate (By similarity).
Gene Name:
OXCT2
Uniprot ID:
Q9BYC2
Molecular weight:
56139.41
Reactions
Succinyl-CoA + a 3-oxo acid → Succinic acid + a 3-oxoacyl-CoAdetails
Succinyl-CoA + Acetoacetic acid → Succinic acid + Acetoacetyl-CoAdetails
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
General function:
Involved in catalytic activity
Specific function:
Catalyzes the ATP- or GTP-dependent ligation of succinate and CoA to form succinyl-CoA. The nature of the beta subunit determines the nucleotide specificity (By similarity).
Gene Name:
SUCLG1
Uniprot ID:
P53597
Molecular weight:
36249.505
Reactions
Guanosine triphosphate + Succinic acid + Coenzyme A → Guanosine diphosphate + Phosphoric acid + Succinyl-CoAdetails
Adenosine triphosphate + Succinic acid + Coenzyme A → ADP + Phosphoric acid + Succinyl-CoAdetails
Inosine triphosphate + Succinic acid + Coenzyme A → IDP + Phosphoric acid + Succinyl-CoAdetails
References
  1. Ostergaard E, Christensen E, Kristensen E, Mogensen B, Duno M, Shoubridge EA, Wibrand F: Deficiency of the alpha subunit of succinate-coenzyme A ligase causes fatal infantile lactic acidosis with mitochondrial DNA depletion. Am J Hum Genet. 2007 Aug;81(2):383-7. Epub 2007 Jun 4. Pubmed: 17668387
General function:
Involved in catalytic activity
Specific function:
Catalyzes the GTP-dependent ligation of succinate and CoA to form succinyl-CoA (By similarity).
Gene Name:
SUCLG2
Uniprot ID:
Q96I99
Molecular weight:
47731.605
Reactions
Guanosine triphosphate + Succinic acid + Coenzyme A → Guanosine diphosphate + Phosphoric acid + Succinyl-CoAdetails
Inosine triphosphate + Succinic acid + Coenzyme A → IDP + Phosphoric acid + Succinyl-CoAdetails
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
General function:
Involved in catalytic activity
Specific function:
Catalyzes the ATP-dependent ligation of succinate and CoA to form succinyl-CoA (By similarity).
Gene Name:
SUCLA2
Uniprot ID:
Q9P2R7
Molecular weight:
50316.88
Reactions
Adenosine triphosphate + Succinic acid + Coenzyme A → ADP + Phosphoric acid + Succinyl-CoAdetails
Guanosine triphosphate + Succinic acid + Coenzyme A → Guanosine diphosphate + Phosphoric acid + Succinyl-CoAdetails
Inosine triphosphate + Succinic acid + Coenzyme A → IDP + Phosphoric acid + Succinyl-CoAdetails
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed: 10592235
General function:
Involved in peptide-aspartate beta-dioxygenase activity
Specific function:
Isoform 1: specifically hydroxylates an Asp or Asn residue in certain epidermal growth factor-like (EGF) domains of a number of proteins. Isoform 8: membrane-bound Ca(2+)-sensing protein, which is a structural component of the ER-plasma membrane junctions. Isoform 8 regulates the activity of Ca(+2) released-activated Ca(+2) (CRAC) channels in T-cells.
Gene Name:
ASPH
Uniprot ID:
Q12797
Molecular weight:
83267.47
Reactions
Peptide L-aspartate + Oxoglutaric acid + Oxygen → peptide 3-hydroxy-L-aspartate + Succinic acid + CO(2)details
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
General function:
Involved in metal ion binding
Specific function:
Hydroxylates HIF-1 alpha at 'Asp-803' in the C-terminal transactivation domain (CAD). Functions as an oxygen sensor and, under normoxic conditions, the hydroxylation prevents interaction of HIF-1 with transcriptional coactivators including Cbp/p300-interacting transactivator. Involved in transcriptional repression through interaction with HIF1A, VHL and histone deacetylases. Hydroxylates specific Asn residues within ankyrin repeat domains (ARD) of NFKB1, NFKBIA, NOTCH1, ASB4, PPP1R12A and several other ARD-containing proteins. Also hydroxylates Asp and His residues within ARDs of ANK1 and TNKS2, respectively. Negatively regulates NOTCH1 activity, accelerating myogenic differentiation. Positively regulates ASB4 activity, promoting vascular differentiation.
Gene Name:
HIF1AN
Uniprot ID:
Q9NWT6
Molecular weight:
40285.25
Reactions
Hypoxia-inducible factor-L-asparagine + Oxoglutaric acid + Oxygen → hypoxia-inducible factor-(3S)-3-hydroxy-L-asparagine + Succinic acid + CO(2)details
Ankyrin-repeat-L-histidine + Oxoglutaric acid + Oxygen → ankyrin-repeat-(3S)-3-hydroxy-L-histidine + Succinic acid + CO(2)details
General function:
Involved in binding
Specific function:
Involved in translocation of malonate, malate and succinate in exchange for phosphate, sulfate, sulfite or thiosulfate across mitochondrial inner membrane
Gene Name:
SLC25A10
Uniprot ID:
Q9UBX3
Molecular weight:
31282.2
References
  1. Ventura FV, Ruiter J, Ijlst L, de Almeida IT, Wanders RJ: Differential inhibitory effect of long-chain acyl-CoA esters on succinate and glutamate transport into rat liver mitochondria and its possible implications for long-chain fatty acid oxidation defects. Mol Genet Metab. 2005 Nov;86(3):344-52. Epub 2005 Sep 19. Pubmed: 16176879
  2. Mizuarai S, Miki S, Araki H, Takahashi K, Kotani H: Identification of dicarboxylate carrier Slc25a10 as malate transporter in de novo fatty acid synthesis. J Biol Chem. 2005 Sep 16;280(37):32434-41. Epub 2005 Jul 15. Pubmed: 16027120
General function:
Involved in transporter activity
Specific function:
High-affinity sodium-dicarboxylate cotransporter that accepts a range of substrates with 4-5 carbon atoms. The stoichiometry is probably 3 Na(+) for 1 divalent succinate
Gene Name:
SLC13A3
Uniprot ID:
Q8WWT9
Molecular weight:
66840.4
References
  1. Oshiro N, Pajor AM: Functional characterization of high-affinity Na(+)/dicarboxylate cotransporter found in Xenopus laevis kidney and heart. Am J Physiol Cell Physiol. 2005 Nov;289(5):C1159-68. Epub 2005 Jun 8. Pubmed: 15944208
  2. Wolff NA, Burckhardt BC, Burckhardt G, Oellerich M, Armstrong VW: Mycophenolic acid (MPA) and its glucuronide metabolites interact with transport systems responsible for excretion of organic anions in the basolateral membrane of the human kidney. Nephrol Dial Transplant. 2007 Sep;22(9):2497-503. Epub 2007 May 25. Pubmed: 17526543
  3. Hagos Y, Steffgen J, Rizwan AN, Langheit D, Knoll A, Burckhardt G, Burckhardt BC: Functional roles of cationic amino acid residues in the sodium-dicarboxylate cotransporter 3 (NaDC-3) from winter flounder. Am J Physiol Renal Physiol. 2006 Dec;291(6):F1224-31. Epub 2006 May 30. Pubmed: 16735460
  4. Yodoya E, Wada M, Shimada A, Katsukawa H, Okada N, Yamamoto A, Ganapathy V, Fujita T: Functional and molecular identification of sodium-coupled dicarboxylate transporters in rat primary cultured cerebrocortical astrocytes and neurons. J Neurochem. 2006 Apr;97(1):162-73. Epub 2006 Mar 8. Pubmed: 16524379
  5. Burckhardt BC, Lorenz J, Kobbe C, Burckhardt G: Substrate specificity of the human renal sodium dicarboxylate cotransporter, hNaDC-3, under voltage-clamp conditions. Am J Physiol Renal Physiol. 2005 Apr;288(4):F792-9. Epub 2004 Nov 23. Pubmed: 15561973
General function:
Involved in oxidoreductase activity
Specific function:
NAD-dependent oxidoreductase with broad substrate specificity that shows both oxidative and reductive activity (in vitro). Has 17-beta-hydroxysteroid dehydrogenase activity towards various steroids (in vitro). Converts 5-alpha-androstan-3-alpha,17-beta-diol to androsterone and estradiol to estrone (in vitro). Has 3-alpha-hydroxysteroid dehydrogenase activity towards androsterone (in vitro). Has retinol dehydrogenase activity towards all-trans-retinol (in vitro). Can convert androsterone to epi-androsterone. Androsterone is first oxidized to 5-alpha-androstane-3,17-dione and then reduced to epi-andosterone. Can act on both C-19 and C-21 3-alpha-hydroxysteroids.
Gene Name:
HSD17B6
Uniprot ID:
O14756
Molecular weight:
35965.41
References
  1. Goel HC, Gupta D, Gupta S, Garg AP, Bala M: Protection of mitochondrial system by Hippophae rhamnoides L. against radiation-induced oxidative damage in mice. J Pharm Pharmacol. 2005 Jan;57(1):135-43. Pubmed: 15639001
  2. Gupta D, Arora R, Garg AP, Bala M, Goel HC: Modification of radiation damage to mitochondrial system in vivo by Podophyllum hexandrum: mechanistic aspects. Mol Cell Biochem. 2004 Nov;266(1-2):65-77. Pubmed: 15646028
  3. Dudkina NV, Eubel H, Keegstra W, Boekema EJ, Braun HP: Structure of a mitochondrial supercomplex formed by respiratory-chain complexes I and III. Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3225-9. Epub 2005 Feb 15. Pubmed: 15713802
  4. Huang LS, Sun G, Cobessi D, Wang AC, Shen JT, Tung EY, Anderson VE, Berry EA: 3-nitropropionic acid is a suicide inhibitor of mitochondrial respiration that, upon oxidation by complex II, forms a covalent adduct with a catalytic base arginine in the active site of the enzyme. J Biol Chem. 2006 Mar 3;281(9):5965-72. Epub 2005 Dec 21. Pubmed: 16371358
  5. Bayley JP, van Minderhout I, Weiss MM, Jansen JC, Oomen PH, Menko FH, Pasini B, Ferrando B, Wong N, Alpert LC, Williams R, Blair E, Devilee P, Taschner PE: Mutation analysis of SDHB and SDHC: novel germline mutations in sporadic head and neck paraganglioma and familial paraganglioma and/or pheochromocytoma. BMC Med Genet. 2006 Jan 11;7:1. Pubmed: 16405730
General function:
Involved in transporter activity
Specific function:
Sodium/sulfate cotransporter that mediates sulfate reabsorption in the kidney
Gene Name:
SLC13A1
Uniprot ID:
Q9BZW2
Molecular weight:
66133.6
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
  3. Lee A, Beck L, Markovich D: The human renal sodium sulfate cotransporter (SLC13A1; hNaSi-1) cDNA and gene: organization, chromosomal localization, and functional characterization. Genomics. 2000 Dec 15;70(3):354-63. Pubmed: 11161786
General function:
Involved in transporter activity
Specific function:
Cotransport of sodium ions and dicarboxylates such as succinate and citrate
Gene Name:
SLC13A2
Uniprot ID:
Q13183
Molecular weight:
64409.5
References
  1. Takahashi R, Ishihara H, Tamura A, Yamaguchi S, Yamada T, Takei D, Katagiri H, Endou H, Oka Y: Cell type-specific activation of metabolism reveals that beta-cell secretion suppresses glucagon release from alpha-cells in rat pancreatic islets. Am J Physiol Endocrinol Metab. 2006 Feb;290(2):E308-16. Epub 2005 Sep 27. Pubmed: 16188913
  2. Hagos Y, Steffgen J, Rizwan AN, Langheit D, Knoll A, Burckhardt G, Burckhardt BC: Functional roles of cationic amino acid residues in the sodium-dicarboxylate cotransporter 3 (NaDC-3) from winter flounder. Am J Physiol Renal Physiol. 2006 Dec;291(6):F1224-31. Epub 2006 May 30. Pubmed: 16735460
  3. Burckhardt BC, Lorenz J, Kobbe C, Burckhardt G: Substrate specificity of the human renal sodium dicarboxylate cotransporter, hNaDC-3, under voltage-clamp conditions. Am J Physiol Renal Physiol. 2005 Apr;288(4):F792-9. Epub 2004 Nov 23. Pubmed: 15561973
  4. Hall JA, Pajor AM: Functional characterization of a Na(+)-coupled dicarboxylate carrier protein from Staphylococcus aureus. J Bacteriol. 2005 Aug;187(15):5189-94. Pubmed: 16030212
General function:
Involved in oxidation reduction
Specific function:
Converts trimethyllysine (TML) into hydroxytrimethyllysine (HTML).
Gene Name:
TMLHE
Uniprot ID:
Q9NVH6
Molecular weight:
44048.895
Reactions
N6,N6,N6-Trimethyl-L-lysine + Oxoglutaric acid + Oxygen → 3-hydroxy-N(6),N(6),N(6)-trimethyl-L-lysine + Succinic acid + CO(2)details
N6,N6,N6-Trimethyl-L-lysine + Oxoglutaric acid + Oxygen → 3-Hydroxy-N6,N6,N6-trimethyl-L-lysine + Succinic acid + Carbon dioxidedetails
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
General function:
Involved in oxidoreductase activity
Specific function:
Dioxygenase that repairs alkylated DNA and RNA containing 1-methyladenine and 3-methylcytosine by oxidative demethylation. Can also repair alkylated DNA containing 1-ethenoadenine (in vitro). Has strong preference for double-stranded DNA. Has low efficiency with single-stranded substrates. Requires molecular oxygen, alpha-ketoglutarate and iron.
Gene Name:
ALKBH2
Uniprot ID:
Q6NS38
Molecular weight:
29322.22
Reactions
DNA-base-CH(3) + Oxoglutaric acid + Oxygen → DNA-base + Formaldehyde + Succinic acid + CO(2)details
General function:
Involved in oxidoreductase activity
Specific function:
Basement membrane-associated chondroitin sulfate proteoglycan (CSPG). Has prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens, especially types IV and V. May be involved in the secretory pathway of cells. Has growth suppressive activity in fibroblasts.
Gene Name:
LEPRE1
Uniprot ID:
Q32P28
Molecular weight:
78921.41
Reactions
L-proline-[procollagen] + Oxoglutaric acid + Oxygen → trans-3-hydroxy-L-proline-[procollagen] + Succinic acid + CO(2)details
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
General function:
Involved in oxidoreductase activity
Specific function:
Shows prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly-sequences in collagens, especially types II, IV and V (By similarity).
Gene Name:
LEPREL1
Uniprot ID:
Q8IVL5
Molecular weight:
60386.32
Reactions
L-proline-[procollagen] + Oxoglutaric acid + Oxygen → trans-3-hydroxy-L-proline-[procollagen] + Succinic acid + CO(2)details
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
General function:
Involved in iron ion binding
Specific function:
Has prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly-sequences in collagens, especially types IV and V (By similarity).
Gene Name:
LEPREL2
Uniprot ID:
Q8IVL6
Molecular weight:
81835.705
Reactions
L-proline-[procollagen] + Oxoglutaric acid + Oxygen → trans-3-hydroxy-L-proline-[procollagen] + Succinic acid + CO(2)details
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
General function:
Involved in oxidoreductase activity
Specific function:
Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
Gene Name:
P4HA3
Uniprot ID:
Q7Z4N8
Molecular weight:
61125.675
Reactions
L-proline-[procollagen] + Oxoglutaric acid + Oxygen → trans-4-hydroxy-L-proline-[procollagen] + Succinic acid + CO(2)details
L-Proline + Oxoglutaric acid + Oxygen → 4-Hydroxyproline + Succinic acid + Carbon dioxidedetails
General function:
Involved in DNA binding
Specific function:
Histone demethylase that specifically demethylates 'Lys-36' of histone H3, thereby playing a central role in histone code. Preferentially demethylates dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. May also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. Required to maintain the heterochromatic state. Associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. Required to sustain centromeric integrity and genomic stability, particularly during mitosis.
Gene Name:
KDM2A
Uniprot ID:
Q9Y2K7
Molecular weight:
81677.13
Reactions
Protein N(6),N(6)-dimethyl-L-lysine + Oxoglutaric acid + Oxygen → protein N(6)-methyl-L-lysine + Succinic acid + Formaldehyde + CO(2)details
Protein N(6)-methyl-L-lysine + Oxoglutaric acid + Oxygen → protein L-lysine + Succinic acid + Formaldehyde + CO(2)details
Protein N6,N6-dimethyl-L-lysine + Oxoglutaric acid + Oxygen → Protein lysine + Succinic acid + Formaldehyde + Carbon dioxidedetails
General function:
Involved in DNA binding
Specific function:
Histone demethylase that demethylates 'Lys-4' and 'Lys-36' of histone H3, thereby playing a central role in histone code. Preferentially demethylates trimethylated H3 'Lys-4' and dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. Preferentially binds the transcribed region of ribosomal RNA and represses the transcription of ribosomal RNA genes which inhibits cell growth and proliferation. May also serve as a substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.
Gene Name:
KDM2B
Uniprot ID:
Q8NHM5
Molecular weight:
144767.43
Reactions
Protein N(6),N(6)-dimethyl-L-lysine + Oxoglutaric acid + Oxygen → protein N(6)-methyl-L-lysine + Succinic acid + Formaldehyde + CO(2)details
Protein N(6)-methyl-L-lysine + Oxoglutaric acid + Oxygen → protein L-lysine + Succinic acid + Formaldehyde + CO(2)details
Protein N6,N6-dimethyl-L-lysine + Oxoglutaric acid + Oxygen → Protein lysine + Succinic acid + Formaldehyde + Carbon dioxidedetails
General function:
Involved in oxidoreductase activity
Specific function:
Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN1 is the most important isozyme under normoxia and, through regulating the stability of HIF1, involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality.
Gene Name:
EGLN1
Uniprot ID:
Q9GZT9
Molecular weight:
46020.585
Reactions
Hypoxia-inducible factor-L-proline + Oxoglutaric acid + Oxygen → hypoxia-inducible factor-trans-4-hydroxy-L-proline + Succinic acid + CO(2)details
General function:
Involved in oxidoreductase activity
Specific function:
Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF2A. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN2 is involved in regulating hypoxia tolerance and apoptosis in cardiac and skeletal muscle. Also regulates susceptibility to normoxic oxidative neuronal death.
Gene Name:
EGLN2
Uniprot ID:
Q96KS0
Molecular weight:
43650.03
Reactions
Hypoxia-inducible factor-L-proline + Oxoglutaric acid + Oxygen → hypoxia-inducible factor-trans-4-hydroxy-L-proline + Succinic acid + CO(2)details
General function:
Involved in oxidoreductase activity
Specific function:
Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF2A. Hydroxylation on the NODD site by EGLN3 appears to require prior hydroxylation on the CODD site. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia. Also hydroxylates PKM in hypoxia, limiting glycolysis. Under normoxia, hydroxylates and regulates the stability of ADRB2. Regulator of cardiomyocyte and neuronal apoptosis. In cardiomyocytes, inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex. In neurons, has a NGF-induced proapoptotic effect, probably through regulating CASP3 activity. Also essential for hypoxic regulation of neutrophilic inflammation. Plays a crucial role in DNA damage response (DDR) by hydroxylating TELO2, promoting its interaction with ATR which is required for activation of the ATR/CHK1/p53 pathway.
Gene Name:
EGLN3
Uniprot ID:
Q9H6Z9
Molecular weight:
27261.06
Reactions
Hypoxia-inducible factor-L-proline + Oxoglutaric acid + Oxygen → hypoxia-inducible factor-trans-4-hydroxy-L-proline + Succinic acid + CO(2)details
General function:
Involved in calcium ion binding
Specific function:
Catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates HIF1A at 'Pro-402' and 'Pro-564'. May function as a cellular oxygen sensor and, under normoxic conditions, may target HIF through the hydroxylation for proteasomal degradation via the von Hippel-Lindau ubiquitination complex.
Gene Name:
P4HTM
Uniprot ID:
Q9NXG6
Molecular weight:
63111.98
Reactions
An HIF alpha chain L-proline + Oxoglutaric acid + Oxygen → An HIF alpha chain trans-4-hydroxy-L-proline + Succinic acid + CO(2)details
General function:
Not Available
Specific function:
Dioxygenase that repairs alkylated single-stranded DNA and RNA containing 3-methylcytosine by oxidative demethylation. Requires molecular oxygen, alpha-ketoglutarate and iron. May have a role in placental trophoblast lineage differentiation (By similarity). Has DNA lyase activity and introduces double-stranded breaks at abasic sites. Cleaves both single-stranded DNA and double-stranded DNA at abasic sites, with the greatest activity towards double-stranded DNA with two abasic sites. DNA lyase activity does not require alpha-ketoglutarate and iron.
Gene Name:
ALKBH1
Uniprot ID:
Q13686
Molecular weight:
43831.39
Reactions
DNA-base-CH(3) + Oxoglutaric acid + Oxygen → DNA-base + Formaldehyde + Succinic acid + CO(2)details
General function:
Not Available
Specific function:
Histone demethylase required for G2/M phase cell cycle progression. Specifically demethylates dimethylated 'Lys-36' (H3K36me2) of histone H3, an epigenetic repressive mark, thereby acting as a transcription activator. Regulates expression of CCNA1 (cyclin-A1), leading to regulate cancer cell proliferation.
Gene Name:
KDM8
Uniprot ID:
Q8N371
Molecular weight:
50851.565
Reactions
Protein N(6),N(6)-dimethyl-L-lysine + Oxoglutaric acid + Oxygen → protein N(6)-methyl-L-lysine + Succinic acid + Formaldehyde + CO(2)details
Protein N(6)-methyl-L-lysine + Oxoglutaric acid + Oxygen → protein L-lysine + Succinic acid + Formaldehyde + CO(2)details
General function:
Not Available
Specific function:
Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase. Is involved in the demethylation of trimethylated 'Lys-9' on histone H3 (H3K9me3), leading to an increase in ribosomal RNA expression. Also catalyzes the hydroxylation of 60S ribosomal protein L27a on 'His-39'. May play an important role in cell growth and survival. May be involved in ribosome biogenesis, most likely during the assembly process of pre-ribosomal particles.
Gene Name:
MINA
Uniprot ID:
Q8IUF8
Molecular weight:
52799.83
Reactions
L-histidine-[60S ribosomal protein L27a] + Oxoglutaric acid + Oxygen → (3S)-3-hydroxy-L-histidine-[60S ribosomal protein L27a] + Succinic acid + CO(2)details
General function:
Not Available
Specific function:
Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase. Specifically demethylates 'Lys-4' (H3K4me) and 'Lys-36' (H3K36me) of histone H3, thereby playing a central role in histone code. Preferentially demethylates trimethylated H3 'Lys-4' (H3K4me3) and monomethylated H3 'Lys-4' (H3K4me1) residues, while it has weaker activity for dimethylated H3 'Lys-36' (H3K36me2). Also catalyzes the hydroxylation of 60S ribosomal protein L8 on 'His-216'. Acts as a regulator of osteoblast differentiation via its interaction with SP7/OSX by demethylating H3K4me and H3K36me, thereby inhibiting SP7/OSX-mediated promoter activation (By similarity). May also play a role in ribosome biogenesis and in the replication or remodeling of certain heterochromatic region. Participates in MYC-induced transcriptional activation.
Gene Name:
NO66
Uniprot ID:
Q9H6W3
Molecular weight:
71084.97
Reactions
Protein N(6),N(6)-dimethyl-L-lysine + Oxoglutaric acid + Oxygen → protein N(6)-methyl-L-lysine + Succinic acid + Formaldehyde + CO(2)details
Protein N(6)-methyl-L-lysine + Oxoglutaric acid + Oxygen → protein L-lysine + Succinic acid + Formaldehyde + CO(2)details
L-histidine-[60S ribosomal protein L8] + Oxoglutaric acid + Oxygen → (3S)-3-hydroxy-L-histidine-[60S ribosomal protein L8] + Succinic acid + CO(2)details
General function:
Not Available
Specific function:
Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3.
Gene Name:
PHF8
Uniprot ID:
Q9UPP1
Molecular weight:
117862.955
Reactions
Protein N(6),N(6)-dimethyl-L-lysine + Oxoglutaric acid + Oxygen → protein N(6)-methyl-L-lysine + Succinic acid + Formaldehyde + CO(2)details
Protein N(6)-methyl-L-lysine + Oxoglutaric acid + Oxygen → protein L-lysine + Succinic acid + Formaldehyde + CO(2)details
General function:
Not Available
Specific function:
Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Might initiate a process leading to cytosine demethylation through deamination into 5-hydroxymethyluracil (5hmU) and subsequent replacement by unmethylated cytosine by the base excision repair system. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. Preferentially binds to CpG-rich sequences at promoters of both transcriptionally active and polycomb-repressed genes. By controlling the levels of 5mC and 5hmC at gene promoters, it may regulate the gene expression silencing induced by cytosine methylation. May have a dual function by also repressing the expression of a subset of genes through recruitment of transcriptional repressors to promoters. Involved in the balance between pluripotency and lineage commitment of cells it plays a role in embryonic stem cells maintenance and inner cell mass cell specification.
Gene Name:
TET1
Uniprot ID:
Q8NFU7
Molecular weight:
235306.965
Reactions
DNA 5-methylcytosine + Oxoglutaric acid + Oxygen → DNA 5-hydroxymethylcytosine + Succinic acid + CO(2)details
General function:
Not Available
Specific function:
Catalyzes the conversion of methylcytosine (5mC) to 5-hydroxymethylcytosine (hmC). Plays an important role in myelopoiesis. The clear function of 5-hydroxymethylcytosine (hmC) is still unclear but it may influence chromatin structure and recruit specific factors or may constitute an intermediate component in cytosine demethylation.
Gene Name:
TET2
Uniprot ID:
Q6N021
Molecular weight:
223809.995
Reactions
DNA 5-methylcytosine + Oxoglutaric acid + Oxygen → DNA 5-hydroxymethylcytosine + Succinic acid + CO(2)details
General function:
Not Available
Specific function:
Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in epigenetic chromatin reprogramming in the zygote following fertilization. Conversion into 5hmC initiates a process leading to cytosine demethylation through deamination into 5-hydroxymethyluracil (5hmU) and subsequent replacement by unmethylated cytosine by the base excision repair system. In zygotes, DNA demethylation occurs selectively in the paternal pronucleus before the first cell division, while the adjacent maternal pronucleus and certain paternally-imprinted loci are protected from this process. Participates in DNA demethylation in the paternal pronucleus by mediating conversion of 5mC into 5hmC. Does not mediate DNA demethylation of maternal pronucleus because of the presence of DPPA3/PGC7 on maternal chromatin that prevents TET3-binding to chromatin (By similarity).
Gene Name:
TET3
Uniprot ID:
O43151
Molecular weight:
179348.305
Reactions
DNA 5-methylcytosine + Oxoglutaric acid + Oxygen → DNA 5-hydroxymethylcytosine + Succinic acid + CO(2)details